The pathophysiology of thermal injury is clearly a sequential interaction between local (burn wound) pathology and systemic organ malfunction that requires study of an integrated profile of continuing injury. These studies are designed to first identify specific responses in the wound as well as systemically, that can be altered only by early pharmacologic intervention. Defining the early physiologic wound responses by the use of the skin flap chamber mode, vascular reactivity, capillary permeability, matrix alteration, and the accompanying chemical changes (burn wound fluid analysis) in the burn wound, and the cause of the immediate systemic hyperglycemia and the subsequent myocardial depression is expected to dictate effective the probable therapeutic interventions. Secondly, local and systemic scavenger, blockers or enhancing therapy will be accomplished by the design of liposomal or ligand drug delivery systems for quantitatively controlled effect. Thirdly, by controlling the early pathophysiologic events coupled with early surgical removal of the burn injury and immediate, permanent coverage, we anticipate eliminating secondary cascade of events perpetuating systemic malfunction. The recently developed on stage in vitro homologous split thickness skin graft will be further developed and employed in both moderate injuries (less than 10%) and in major burn injuries (greater than 30% burns).